Selective monoamine reuptake inhibitors, and in particular serotonin reuptake inhibitors (SSRI's), are the gold standard for treating depression. However, their most severe drawback is that while the side effects set in almost immediately, no substantial antidepressant effect will be seen within the first 2 to 4 weeks, leaving a window of vulnerability during which the patent might be non-compliant with therapy. While co-administration of fast-acting antidepressants may overcome this, it is more preferable to counteract the self-inhibitory mechanism that delays onset of SSRI effects.
There are good indications that this may be achieved by blocking certain receptors that down-regulate the discharge of serotonin as the concentration of neurotransmitter in the synaptic cleft rises. Thus WO 96/33710 (Astra) describes a combination of a 5-HT uptake inhibitor with a selective 5-HT1A antagonist, and WO 00/15217 (AstraZeneca), WO 00/15218 (AstraZeneca) and WO 00/15219 (AstraZeneca) disclose specific examples of such combinations.
Another combination involving nicotinic ligands, however for a quite different use, is disclosed in WO 00/45846 (Synthelabo). This patent publication describes the use of nicotine or a nicotinic ligand in combination with a monoamine oxidase (MAO) inhibitor for the treatment of tobacco withdrawal symptoms, which combination shows reduced cardiovascular side effects.
Finally WO 00/25783 (Carlsson & Carlsson) describes the use of a nicotinic receptor agonist in the treatment of obsessive compulsive disorder (OCD). A combination therapy and the treatment of other affective disorders are not described.